| Project/Area Number |
18K19722
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
Kanzaki Makoto 東北大学, 医工学研究科, 准教授 (10272262)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 運動 / 骨格筋 / 代謝 / 免疫 / イメージング / マイオカイン / GLUT4 / 好中球 / 運動免疫 / 糖代謝 |
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| Outline of Final Research Achievements |
By establishing a novel intravital imaging system, we successfully revealed the importance of intramuscular paracrine/autocrine systems involving contracting myofibers, adjacent vascular endothelial cells and recruited neutrophils, which are triggered by muscle contractile activity and reliant upon CX3CL1/fractalkine-mediated signals. Specifically, the intravital imaging using transgenic mouse harboring skeletal muscle-specific GLUT4-EGFP expression and Quantum-dot-labelled neutrophils demonstrated that the fractalkine-mediated signals are required for both neutrophil accumulation and enhanced GLUT4 translocation in the working skeletal muscles. It is thus concluded that fractalkine is a key factor for organizing a neutrophil‐mediated favorable immunometabolic niche by orchestrating intramuscular vascular and immune responses in working skeletal muscles.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって新たに開発した「運動筋ニッチにおける免疫代謝微小環境の生体イメージング解析システム」は、活動中の骨格筋内局所において惹起される異種細胞間の機能連携とその生理的重要性を理解する上で極めて有用な優れた解析系である。広範な骨格筋研究へと応用が可能であり、筋研究領域に多大な貢献をもたらすと期待される。また、本研究により運動筋ニッチがつかさどる運動免疫ネットワーク制御機構の一端を明らかにできた。今後、2型糖尿病などの生活習慣病、ロコモ、加齢時における「運動筋ニッチ」の状態を精査していくことで、病態生理的観点からも「運動筋ニッチ」の重要性を明らかになれば、新規の治療標的となる可能性が高い。
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